Porcine parvovirus is an autonomous replicating virus of the Parvovirinae subfamily of the genus Protoparvovirus within the family Parvoviridae containing a single stranded DNA molecule of about 5100 nucleotides (Cotmore et al., 2014: Arch Virol.: 159(5): 1239-1247; Molitor et al., 1984: Virology: 137(2):241-54). Only the minus strand of the DNA is packaged into virions. The genome of the virus encodes three capsid proteins (VP1, VP2, VP3) and one non-structural protein (NS1). The capsid of parvovirus is about 22-25 nanometers in diameter and is comprised of VP1 and VP2 subunits. These proteins are derived from alternatively spliced versions of the same RNA molecule and thus overlap in sequence. Further, porcine parvovirus exhibits a high level of sequence similarity to feline panleukopenia virus, canine parvoviruses and rodent parvovirus (Ranz et al., 1989: J. gen. Virol: 70:2541-2553).
Although there are differences in porcine parvovirus strains, some being extremely pathogenic and others being less pathogenic or totally non-pathogenic, when the virus becomes established or endemic in a country, the pathogenic strains appear to circulate in the population.
Porcine parvovirus (PPV) infection is a common cause of reproductive failure in breeding pigs throughout the world. Serological studies show that porcine parvovirus is widespread in all swine producing regions of the world with up to 80% of animals showing seroconversion.
The Porcine Parvovirus (PPV) causes reproductive failure in swine, resulting in death and fetal mummification, still births and other reproductive failures in pregnant sows. (Joo & Johnson. 1976. Veterinary Bulletin 46, 653-660; Mengeling. 1978. J. Am. Vet. Med. Assoc. 172, 1291-1294).
The PPV induces reproductive failure when susceptible (non-immune) gilts and sows are infected during pregnancy. This is the only time the virus causes disease. Infection in the pig occurs following ingestion or inhalation of the virus. The PPV then circulates in the bloodstream, and in the pregnant pig crosses the placenta and infects the developing embryos and fetuses. Following natural infection, active immunity develops that probably lasts for the life of the pig. If active immunity occurs before pregnancy then the developing piglets are not affected. At birth the piglets receive maternal immunity in the colostrum from the sow and this maternal immunity lasts for up to 20 weeks of age. The greater the level of active immunity in the sow, the more maternal immunity that she passes onto her piglets. Thereafter, natural infection with PPV may occur.
The disease caused by PPV in pigs is often referred to as a SMEDI (an acronym of stillbirth, mummification, embryonic death, and infertility). If infection occurs at days 0-30 of pregnancy, embryonic mortality may occur resulting in decreased litter size. The most obvious feature following infection at 30-70 days of pregnancy is the birth of mummified piglets. Mummification is the process of sterile digestion of the tissues of the piglets that die in the uterus after the skeleton has started to solidify. PPV infection is also associated with stillbirths and weak born pigs if infection occurs in the later stages of pregnancy. Abortion may also be the result of PPV infection, but is not a common clinical sign of this disease. Overall, PPV infection decreases the number of pigs born per sow per year.
Currently available PPV vaccines are produced by growing native virus on primary cells of porcine origin or in established cell lines. After this, infectious virus is isolated and inactivated with chemical agents to end up with a whole cell killed virus vaccine. However, such processes of growing native infectious virus is problematic for biosecurity and safety considerations. Therefore, there is a need for recombinant PPV vaccines.
Subunit vaccines based on recombinant proteins can suffer from poor immunogenicity owing to incorrect folding of the target protein or poor presentation to the immune system. Further, whole cell killed vaccines present all antigens of the native virus, whereas in a subunit vaccine there is a limitation to a specific amino acid sequence.
Recombinant PPV vaccines have been already described in the prior art, however, until now only whole cell killed vaccines are commercially available. Thus, it seems that so far no appropriate recombinant PPV subunit vaccines have been developed and shown to be effective and safe. The recombinant PPV subunit vaccines described so far have not been tested in controlled, laboratory challenge experiments. The recombinant PPV subunit vaccines that have been evaluated, have not worked as well as whole cell killed PPV vaccines or the recombinant PPV subunit vaccines have not been safe (shown adverse reactions). Therefore, there is still a need for recombinant PPV subunit vaccines being highly effective and safe.
Field isolates of porcine parvovirus (PPV) have been identified that differ genetically and antigenically from the vaccine strains. PPV Genotype 2 virus, PPV-27a, is highly virulent in pregnant gilts after experimental infection, as demonstrated by the high mortality among the fetuses of sows infected with PPV-27a (85%) compared with sows infected with the other strains of PPV, e.g. PPV-NADL-2. However, the currently available commercial vaccines against PPV are based on inactivated whole-virus preparations of PPV genotype 1 strains isolated some 30 years ago (Jozwik et al 2009; Journal of General Virology; 90; 2437-2441). Thus, there is a need for new vaccines protecting against new highly virulent pathogenic strains of PPV that better match PPV in the field.
Further prior art is as follows:
EP 0 551 449 A1 discloses a method for producing a VP2 subunit vaccine against porcine parvovirus.
Cadar D et al. (Infection, Genetics and Evolution 2012, 12: 1163-1171) describe the phylogeny and evolutionary genetics of porcine parvovirus in wild boars.
Streck A F et al. (Journal of General Virology 2011, 92: 2628-2636) describe the high rate of viral evolution in the capsid protein of porcine parvovirus.
WO 88/02026 relates to empty viral capsid vaccines.
Martinez C et al. (Vaccine 1992, 10(10): 684-690), discloses the production of porcine parvovirus empty capsids with high immunogenic activity.
Xu F et al. (Applied and Environmental Microbiology 2007, 73(21): 7041-7047) describe the induction of immune responses in mice after intragastric administration of Lactobacillus casei producing porcine parvovirus VP2 protein.
Moreover, there is a need for new and better vaccines against extremely pathogenic strains of PPV giving a broader protection against different (heterologous) strains (cross-protection) of PPV.